DegronMD - O14672(ADAM10)

FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:26686862, PubMed:11786905, PubMed:29224781). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146). {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:11786905, ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:29224781}.; FUNCTION: (Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores. {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:30463011}. View more >>

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GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S337L	TCGA-CF-A27C	BLCA	TCGA	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.0833
p.S337L	DO828	BLCA	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.0833
p.E403K	TCGA-CG-5734	STAD	TCGA	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1667
p.E403K	DO38265	STAD	ICGC	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1667
p.S423F	TCGA-DK-A2I1	BLCA	TCGA	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.0556
p.S423F	DO444	BLCA	ICGC	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.0556
p.G342E	TCGA-DU-6393	LGG	TCGA	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.2222
p.G342E	DO22149	LGG	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.2222
p.T360I	TCGA-ER-A19S	SKCM	TCGA	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.1111
p.T360I	DO47380	SKCM	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.1111
p.P401L	TCGA-G4-6297	COAD	TCGA	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1111
p.P401L	DO9418	COAD	ICGC	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1111
p.E403Q	TCGA-IR-A3LL	CESC	TCGA	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1667
p.E403Q	DO44362	CESC	ICGC	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1667
p.L349F	TCGA-J9-A8CK	PRAD	TCGA	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation altering degron motif	0.6981
p.L349F	DO223660	PRAD	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation altering degron motif	0.6981
p.P401T	DO228976	LICA	ICGC	QKENG	DEG_APCC_KENBOX_2	409:413	Mutation rewiring degron network	0.1111
p.R355M	DO24596	LUAD	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation substituting flanking lysine	0.3611
p.R343Q	DO26596	LUSC	ICGC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.25
p.L358V	SIDM01588	Endometrial Carcinoma	GDSC	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.1667
p.L358V	ACH-000993	Endometrial/Uterine Cancer	CCLE	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation rewiring degron network	0.1667
p.S347I	ACH-002027	Endometrial/Uterine Cancer	CCLE	KSKLYSD	LIG_APCC_ABBAyCdc20_2	346:352	Mutation altering degron motif	0.623

DegronMD: protein-targeted degradation, mutation and drug response to degrons

ADAM10

UniProt ID: O14672

Entrez ID: 102

Protein name: Disintegrin and metalloproteinase domain-containing protein 10 (ADAM 10) (EC 3.4.24.81) (CDw156) (Kuzbanian protein homolog) (Mammalian disintegrin-metalloprotease) (CD antigen CD156c)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ADAM10 in